The affects of serotonin(5-hydroxytryptamine or 5-HT) have been the focus of many studies ranging from memory loss during aging to mental retardation in Down Syndrome1,2. Irregular 5-HT levels cause insomnia, improper digestion, decrease in libido, migraine headaches, learning disorders and schizophrenia. The most common 5-HT studies link the decrease in 5-HT brain levels with the psychological effects of depression3. The objective of this study is to determine if brain 5-HT levels and the mood of stress-vulnerable subjects can be improved through a diet that is rich in tryptophan (W)4.
To determine the effectiveness of tryptophan as a 5-HT promoter, the results of dietary consumption of alpha-lactalbumin, a bovine milk whey protein with high tryptophan content, were analyzed. Although tryptophan is the least abundant amino acid in foods, alpha-lactalbumin contains the highest tryptophan content of all bovine fractions5. This advantage given to tryptophan for brain access will significantly increase the rate of 5-HT synthesis. The synthesis of 5-HT begins with tryptophan.
Tryptophan (figure 1) is an essential amino acid, which means the body is incapable of synthesizing tryptophan; tryptophan must be acquired from dietary intake6. Rich amounts of tryptophan can be found in foods like turkey, chicken, yogurt, bananas, peanut butter, avocado, pineapple and unripened cheese. On an average, the body requires only 10 milligrams (mg) of tryptophan at one time in order to prevent diseases and conditions associated with tryptophan depletion7.
The conversion of tryptophan to 5-HT is a two step process (figure 2). The actual synthesis, however, begins with facilitated transport of tryptophan from the blood to the brain. The entry of tryptophan to the brain depends on the tryptophan blood concentration as well its ratio concentration to that of other neutral amino acids which it competes for brain access8. Once tryptophan has reached the brain, 5-HT neurons containing the enzyme tryptophan hydroxylase convert tryptophan to 5-hydroxytryptophan (5-HTP). This is the first step in 5-HT synthesis. Inhibition of this step by p-chlorophenylalanine (PCPA)9 and other inhibitors greatly reduce 5-HT synthesis and blood-brain barrier permeability (BBB)10. 5-HTP is transported through the blood more rapidly than tryptophan, and more easily penetrates the BBB. Once 5-HTP has crossed the BBB, aromatic amino acid decarboxylase, converts 5-HTP to 5-HT and 5-HT is concealed in vesicles to be stored in the neuron terminal for future use. Some tryptophan is converted to 5-HTP in the intestinal tract and can be transported to the brain for further synthesizing. 5-HTP is transported through the blood more rapidly than tryptophan, and can more easily penetrate the BBB.
5-HT is an inhibitory monoamine neurotransmitter, present in only minute amounts in the brain11,12. The majority of 5-HT present in the brain is produced in the brain, working to produce calm, soothing, and euphoric feelings within the body. As the brain's primary neurotransmitter, 5-HT is responsible for such functions as memory, appetite, hormone and body temperature regulation, digestion, sleep promotion, mood and many other cognitive body functions13. The body contains 14 different 5-HT receptors that are organized into seven different classes. 5-HT producing neurons form the largest and most complex efferent system in the brain8, and can be found throughout the entire central nervous system (CNS). The 5-HT receptors located in the CNS are divided into two subtypes, 5HT1 and 5-HT2. Most 5-HT receptors use adenyl cyclase (AC) as an enzyme linked with a stimulatory G protein (Gs) which increase the concentration of cyclic adenosine 3', 5'monophosphate (cAMP)14. Other enzymes use an inhibitory G protein (Gi), which decrease the cAMP concentration. The inhibition of ligand binding to the 5-HT receptors will decrease 5-HT concentrations.
Under stress, the body's nervous system attempts to compensate for the change in homeostasis15. When a threat is perceived, the sympathetic nervous system (SNS) immediately stimulates a response: Pupils dilate; the heart rate is increased; the bronchi expand to increase oxygen consumption; blood pressure is increased; intestinal contractions are inhibited, and the adrenal medulla secretes the catecholamines, epinephrine and norepinephrine. The parasympathetic nervous system (PNS) responds to counteract the responses of the SNS by secreting 5-HT and other neurotransmitters, helping the body return to its normal state. 5-HT plays an integral role in this counteraction by acting as a balancing chemical. 5-HT inhibits the release of adrenocorticotropic hormone (ACTH), which promotes secretion of cortisol directly into the blood stream16,17. Prolactin is secreted in direct response to serotonergic mechanisms in the brain18.
Because the decrease of 5-HT concentrations in the cerebrum are associated with mood disorders such as depressions, it is presumed that the increase of 5-HT cerebral activity will improve mood under stress. In order to effectively conclude the increase of cerebral 5-HT concentration under stress is due to the presence of a high tryptophan diet, several test subjects were observed and monitored after controlled, stress-induced experiments and consumption of either a casein or an alpha-lactalbumin diet. The effects of stress and dietary intake were observed via alteration of mood, skin conductance, pulse rate, cortisol concentrations and changes in the plasma ratio of tryptophan to the other large neutral amino acids(LNAA).
Several university students were selected to participate in the study. Each student filled out a personal questionnaire and a form called the Inadequacy Scale of the Dutch Personality Inventory (IN), which measures neuroticism19. A statistical analysis performed on the IN identified students with scores in the high quartile as high stress (HS) and those in the low quartile as low stress (LS). A battery of computer assisted tests under various time constraints were administered to each subject after consumption of a prescribed diet. The diets consisted of bread, margarine, fruit jelly, tea, coffee, a candy bar, grape juice, and a chocolate drink and the subjects were supervised to ensure complete consumption. The diets differed only with the exception of the chocolate drink in which the chocolate drink contained the addition of either alpha-lactalbumin or casein(Table 1). The total energy composition of each diet was 7995 and 7996 kilojoules (kj) respectively, making the diets isoenergetic (Table 2).
The two-day experiment began with a fast the previous night in which the subjects were only allowed to consume water or tea with no sugar. Upon arrival at the testing site, the subjects remained sedentary and were only allowed to read. The breakfast diet was given readily on arrival and a snack and lunch followed one hour and fifteen minutes and forty-five minutes later, respectively. One hour and thirty minutes after lunch, a salivary cortisol20 sample was taken followed three minutes later by a blood sample. The subjects were then placed in a temperature-controlled room in front of a computer and given experimental instructions. Electrodes were used while instructions were given to subjects to measure pulse rate and skin conductance. These readings were retained as baseline readings. The series of stress tests were applied using the computer, and each test consisted of a four minute Profile of Mood States (POMS), and a twenty-five minute mental arithmetic task followed by a four minute version of POMS. The POMS test measured changes in five moods divided into two subclasses, positive and negative21. Vigor is considered a positive mood while anger, depression, fatigue, and tension are considered negative moods. The POMS questionnaire consisted of a five-point scale ranging from "strongly disagree" to "strongly agree". To show the effects of uncontrollable stress, the arithmetic task consisted of eighteen, one-minute consecutive trials while subjected to different levels of noise at 65,70, or 80 decibels. Several multiple-choice questions were present at one time and the subject was told a minimum number of answers had to be answered correctly in order to control the noise level for the next trial. The test was manipulated to ensure the criterion was not met, thus inflicting experimental stress. The results of the POMS test are analyzed by repeated-measured multivariate (MANOVA) and univariate analyses of variance (ANOVA). MANOVA analyzes the relationship between experimental stress and diet measuring the effects of experimental stress on pulse rate, skin conductance and cortisol concentration, and ANOVA analyzes stress vulnerability between HS and LS subjects. Salivary cortisol samples were taken twenty-five minutes after the onset of stress and thirty-five minutes after the test was completed. After completion of the test, the results of each subject were compared. The tryptophan plasma ratio to the LNAA after consumption of the alpha-lactalbumin in both HS and LS subjects revealed a 48% increase as opposed to the casein diet.
Skin conductance and pulse rate of HS and LS subjects during stress were significantly increased after the alpha-lactablumin diet. The MANOVA analysis showed direct interaction between stress vulnerability with diet and experimental stress from a change in cortisol concentration. Cortisol secretions in HS subjects were prevented after alpha-lactalbumin diet consumption, where as these effects were not seen in LS subjects. The ANOVA analysis of prolactin concentration indicates that prolactin secretions depend on the vulnerability of the subject to stress. The prolactin secretions of HS subjects increased by 40% after consumption of the alpha-lactalbumin diet, where as LS subjects showed no significant change.
The analysis of the POMS scale showed the affects of acute stress after dietary consumption. Feelings of anger in HS and LS subjects increased after consumption of both diets, whereas the change in tension for LS subjects was insignificant. A higher ratio of fatigue was exhibited in the mood of HS subjects, and lower ratio of vigor as compared to LS. The vulnerability to a depressive mood increased in HS subjects after the casein diet but declined after the alpha-lactalbumin diet. No effect was found in LS subjects.
In general, the rates of synthesis by brain neurons depend considerably on the amino acid availability to the brain in respect to each dietary precursor. The precursor dependence seems to correspond to the unsaturation of the enzyme catalyzing the rate-limiting step with substrate at normal brain concentrations22. The precursor induces increases in brain transmitter formation and thus influences a variety of behaviors, indicating transmitter activity has been increased.
Since the alpha-lactalbumin diet contains a greater tryptophan content in comparison to the casein diet, the alpha-lactalbumin diet increases the tryptophan plasma ratio to that of the other LNAA by a two to one (2:1) ratio (Table 3). This ratio establishes the relationship between a high tryptophan diet and a decrease in depressive mood. This relationship, however, appears only to be established in HS subjects because the physiological effects of stress as well as the endocrine effects only exude significant changes when the subject is vulnerable to stress and administered a diet designed to promote high 5-HT synthesis. The conclusion that consumption of a diet containing high tryptophan content reduces cortisol concentrations and improves mood under stress only applies if the patient is extremely vulnerable (HS) to stress. Dietary effects on LS subjects under either acute or chronic stress do not show enough evidence to indicate that the presence of alpha-lactalbumin increases the plasma trytophan ratio significantly. The ability to cope with stress for HS subjects is therefore attributed to the amount of tryptophan content in the alpha-lactalbumin diet.
Copyright © 2002 Lateefah Davis and Koni Stone
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